1. Field of the Invention
This invention relates to an acid addition salt of 2-phenyl-6-(1-hydroxy-2-t-butylaminoethyl)-4H-pyrido[3,2-d]-1,3-dioxin and to a process for its preparation. More specifically, it relates to the maleic acid salt of said compound, and to a process for its preparation, particularly in crystalline form.
2. Description of the Prior Art
Belgian Patent 823,616, granted June 20, 1975, describes the preparation of 2-hydroxymethyl-3-hydroxy-6-(1-hydroxy-2-t-butylaminoethyl)-pyridine (formula IV), a bronchodilator, by the following three related sequences: ##STR1##
In the above formulae, each of R and R' is phenyl or methyl; and Z is --CHOH--CH.sub.2 --NH--C(CH.sub.3).sub.3.
The reaction sequence IA .fwdarw. IB .fwdarw. IV affords good yields of the final product (IV) but suffers from the economic disadvantage of requiring catalytic hydrogenation to remove the benzyl group. Further, preparation of the starting benzyl ether (IA) requires benzyl bromide, a relatively expensive substance, as reactant.
Reaction sequence IIIA .fwdarw. IIIB .fwdarw. IV is less attractive from an economic standpoint than is sequence IIA .fwdarw. IIB .fwdarw. IV because of the relatively high costs realized in the preparation of reactant IIIA.
The sequence IIA .fwdarw. IIB .fwdarw. IV is free of the above disadvantages. However, on large scale operation it, as are the other two sequences, is subject to formation of colored impurities in the amination step. Its presence, along with that of other substances, coupled with the fact that for convenience and economy of large scale operation the intermediates are not purified, leads to formation of colored impurities. In sequence IIA .fwdarw. IIB .fwdarw. IV these impurities interfere in the isolation, recovery and purification of intermediate IIB and final product IV. The impurities appear to arise, in part at least, from the presence of iodide introduced via trimethylsulfonium iodide in the preparation of the epoxides (IA, IIA, IIIA).